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The stem cell organisation, and the proliferative and gene expression profile of Barrett's epithelium, replicates pyloric-type gastric glands

The stem cell organisation, and the proliferative and gene expression profile of Barrett's epithelium, replicates pyloric-type gastric glands
The stem cell organisation, and the proliferative and gene expression profile of Barrett's epithelium, replicates pyloric-type gastric glands
Objective

Barrett's oesophagus shows appearances described as ‘intestinal metaplasia’, in structures called ‘crypts’ but do not typically display crypt architecture. Here, we investigate their relationship to gastric glands.

Methods

Cell proliferation and migration within Barrett's glands was assessed by Ki67 and iododeoxyuridine (IdU) labelling. Expression of mucin core proteins (MUC), trefoil family factor (TFF) peptides and LGR5 mRNA was determined by immunohistochemistry or by in situ hybridisation, and clonality was elucidated using mitochondrial DNA (mtDNA) mutations combined with mucin histochemistry.

Results

Proliferation predominantly occurs in the middle of Barrett's glands, diminishing towards the surface and the base: IdU dynamics demonstrate bidirectional migration, similar to gastric glands. Distribution of MUC5AC, TFF1, MUC6 and TFF2 in Barrett's mirrors pyloric glands and is preserved in Barrett's dysplasia. MUC2-positive goblet cells are localised above the neck in Barrett's glands, and TFF3 is concentrated in the same region. LGR5 mRNA is detected in the middle of Barrett's glands suggesting a stem cell niche in this locale, similar to that in the gastric pylorus, and distinct from gastric intestinal metaplasia. Gastric and intestinal cell lineages within Barrett's glands are clonal, indicating derivation from a single stem cell.

Conclusions

Barrett's shows the proliferative and stem cell architecture, and pattern of gene expression of pyloric gastric glands, maintained by stem cells showing gastric and intestinal differentiation: neutral drift may suggest that intestinal differentiation advances with time, a concept critical for the understanding of the origin and development of Barrett's oesophagus.
1468-3288
1854-1863
Lavery, Danielle L.
048fe0ad-8ad7-457d-a13b-8e4c0d2e1bab
Nicholson, Anna M.
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Poulsom, Richard
739a17cf-14a4-44d6-9fdd-d70f18d99a10
Jeffery, Rosemary
57f312e1-86d7-4008-abe3-b64809ef943e
Hussain, Alia
5094694f-5a1b-4791-bbe7-75abd0b21672
Gay, Laura J.
12fdcc7e-a6ab-44fe-9e91-d84f0dee0a17
Jankowski, Janusz A.
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Zeki, Sebastian S.
30e07c3b-9cdb-4706-acba-7c61fd5805cb
Barr, Hugh
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Harrison, Rebecca
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Going, James
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Kadirkamanathan, Sritharan
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Davis, Peter
20400357-d5c9-4b02-89f0-8ecf5c9ebb36
Underwood, Timothy
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Novelli, Marco R.
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Rodriguez-Justo, Manuel
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Shepherd, Neil
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Jansen, Marnix
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Wright, Nicholas A.
85ea5c1c-0f38-4038-8a98-535dafe86a20
McDonald, Stuart A.C.
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Lavery, Danielle L.
048fe0ad-8ad7-457d-a13b-8e4c0d2e1bab
Nicholson, Anna M.
8d89872c-9bca-4331-bf30-257a2f864f49
Poulsom, Richard
739a17cf-14a4-44d6-9fdd-d70f18d99a10
Jeffery, Rosemary
57f312e1-86d7-4008-abe3-b64809ef943e
Hussain, Alia
5094694f-5a1b-4791-bbe7-75abd0b21672
Gay, Laura J.
12fdcc7e-a6ab-44fe-9e91-d84f0dee0a17
Jankowski, Janusz A.
1d38796a-b148-4287-b79c-e8bbafcebc50
Zeki, Sebastian S.
30e07c3b-9cdb-4706-acba-7c61fd5805cb
Barr, Hugh
d9616fd6-936c-40c5-a4b8-ec37ae3d3bde
Harrison, Rebecca
c91003a5-f6e8-4a9a-b8f3-e32232960f50
Going, James
db538066-fe87-4efa-a022-a2ff4f348d8a
Kadirkamanathan, Sritharan
a46727da-c0a3-42a1-bb89-c94c19597bf6
Davis, Peter
20400357-d5c9-4b02-89f0-8ecf5c9ebb36
Underwood, Timothy
8e81bf60-edd2-4b0e-8324-3068c95ea1c6
Novelli, Marco R.
1e3ab514-76a6-4c59-9a5d-499ec7d34ced
Rodriguez-Justo, Manuel
27e64c59-84ff-46d7-b8a3-4aa1c00473bd
Shepherd, Neil
b593f04f-79c0-4824-8fac-36538611194e
Jansen, Marnix
d819908a-feef-45a2-9531-f040c2d1991e
Wright, Nicholas A.
85ea5c1c-0f38-4038-8a98-535dafe86a20
McDonald, Stuart A.C.
64a29c16-0239-48ab-9346-8306297761b3

Lavery, Danielle L., Nicholson, Anna M., Poulsom, Richard, Jeffery, Rosemary, Hussain, Alia, Gay, Laura J., Jankowski, Janusz A., Zeki, Sebastian S., Barr, Hugh, Harrison, Rebecca, Going, James, Kadirkamanathan, Sritharan, Davis, Peter, Underwood, Timothy, Novelli, Marco R., Rodriguez-Justo, Manuel, Shepherd, Neil, Jansen, Marnix, Wright, Nicholas A. and McDonald, Stuart A.C. (2014) The stem cell organisation, and the proliferative and gene expression profile of Barrett's epithelium, replicates pyloric-type gastric glands. Gut, 63 (12), 1854-1863. (doi:10.1136/gutjnl-2013-306508). (PMID:24550372)

Record type: Article

Abstract

Objective

Barrett's oesophagus shows appearances described as ‘intestinal metaplasia’, in structures called ‘crypts’ but do not typically display crypt architecture. Here, we investigate their relationship to gastric glands.

Methods

Cell proliferation and migration within Barrett's glands was assessed by Ki67 and iododeoxyuridine (IdU) labelling. Expression of mucin core proteins (MUC), trefoil family factor (TFF) peptides and LGR5 mRNA was determined by immunohistochemistry or by in situ hybridisation, and clonality was elucidated using mitochondrial DNA (mtDNA) mutations combined with mucin histochemistry.

Results

Proliferation predominantly occurs in the middle of Barrett's glands, diminishing towards the surface and the base: IdU dynamics demonstrate bidirectional migration, similar to gastric glands. Distribution of MUC5AC, TFF1, MUC6 and TFF2 in Barrett's mirrors pyloric glands and is preserved in Barrett's dysplasia. MUC2-positive goblet cells are localised above the neck in Barrett's glands, and TFF3 is concentrated in the same region. LGR5 mRNA is detected in the middle of Barrett's glands suggesting a stem cell niche in this locale, similar to that in the gastric pylorus, and distinct from gastric intestinal metaplasia. Gastric and intestinal cell lineages within Barrett's glands are clonal, indicating derivation from a single stem cell.

Conclusions

Barrett's shows the proliferative and stem cell architecture, and pattern of gene expression of pyloric gastric glands, maintained by stem cells showing gastric and intestinal differentiation: neutral drift may suggest that intestinal differentiation advances with time, a concept critical for the understanding of the origin and development of Barrett's oesophagus.

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More information

Published date: December 2014
Organisations: Cancer Sciences

Identifiers

Local EPrints ID: 362615
URI: http://eprints.soton.ac.uk/id/eprint/362615
ISSN: 1468-3288
PURE UUID: 767ecbcf-2a43-4476-a0d8-e8812af0272b
ORCID for Timothy Underwood: ORCID iD orcid.org/0000-0001-9455-2188

Catalogue record

Date deposited: 27 Feb 2014 16:50
Last modified: 15 Mar 2024 03:17

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Contributors

Author: Danielle L. Lavery
Author: Anna M. Nicholson
Author: Richard Poulsom
Author: Rosemary Jeffery
Author: Alia Hussain
Author: Laura J. Gay
Author: Janusz A. Jankowski
Author: Sebastian S. Zeki
Author: Hugh Barr
Author: Rebecca Harrison
Author: James Going
Author: Sritharan Kadirkamanathan
Author: Peter Davis
Author: Marco R. Novelli
Author: Manuel Rodriguez-Justo
Author: Neil Shepherd
Author: Marnix Jansen
Author: Nicholas A. Wright
Author: Stuart A.C. McDonald

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